What question did this study set out to answer?

This study aims to compare the efficacy of Ustekinumab, Tofacitinib, and Upadacitinib in patients with ulcerative colitis who have previously failed advanced therapies.

January 23, 2026

P0625TRIDENT-UC Study: Higher Efficacy Medication in Bio-Exposed Ulcerative Colitis Patients

Key Points

This study aims to compare the efficacy of Ustekinumab, Tofacitinib, and Upadacitinib in patients with ulcerative colitis who have previously failed advanced therapies.
Conducted a retrospective analysis involving 312 ulcerative colitis patients across 9 centers.
Patients were divided into three treatment groups: Ustekinumab, Tofacitinib, and Upadacitinib.
Assessed outcomes at 16 and 52 weeks focusing on steroid-free clinical remission and endoscopic remission.
Utilized multivariable models to adjust for demographics, disease activity, and prior treatments.
At week 16, Upadacitinib had 4 times higher odds of achieving steroid-free clinical remission compared to Ustekinumab.
At week 52, Upadacitinib maintained 3 times higher odds of remission than both Ustekinumab and Tofacitinib.
Upadacitinib achieved higher rates of endoscopic remission compared to the other medications at both weeks.
In subanalysis, Upadacitinib showed superior outcomes after anti-TNF failure compared to the other therapies.

Abstract

Abstract Background Despite the progress in advanced therapies (AT) for ulcerative colitis (UC), selecting a second-line treatment after failure remains challenging. Recent guidelines recommend Ustekinumab (UST), Tofacitinib (TOFA), or Upadacitinib (UPA) as high-efficacy options after prior AT failure. However, no real-world studies have compared all three therapies simultaneously. Methods Retrospective multicentre study (9 centres) of UC patients who failed ≥1 AT. Patients were stratified into UST, TOFA, or UPA groups and assessed at 16 and 52 weeks. The primary outcome was steroid-free clinical remission (SFCR) based on the Patient Reported Outcomes-2. Secondary outcomes included biochemical remission based on faecal calprotectin levels and endoscopic remission (Mayo Endoscopic Subscore = 0). A subanalysis assessed only second-line therapy after anti-TNF failure. Multivariable models were adjusted for demographics, disease activity and prior treatments. Results We evaluated 312 patients 57.1% female (n = 178); mean age at diagnosis 32.6 ± 8.4 years who initiated UST (n = 135; 43.3%), UPA (n = 103; 33.0%), or TOFA (n = 74; 23.7%). Baseline disease duration and extent were comparable across groups, and 53.2% (n = 166) had failed ≥2 prior advanced therapies. In the multivariate model, at week 16, UPA had 4 times higher odds of achieving SFCR than UST (OR 3.89; p 0.001) and 2 times compared to TOFA (OR 2.31; p = 0.016). At week 52, UPA showed 3 times higher odds of SFCR than UST (OR 3.34; p = 0.003) and than TOFA (OR 2.72; 0.039). UPA also achieved higher endoscopic remission at week 16 and 52 compared to UST (16w: OR 2.47; p = 0.036; 52w: OR 5.95; p 0.001) and TOFA (16w: OR 5.42; p = 0.001; 52w: OR 2.64; p = 0.049). Post-hoc comparisons from the linear mixed-effects model showed that UPA achieved a higher reduction in faecal calprotectin than UST (p 0.001) and TOFA (p = 0.044). In the subanalysis, UPA was superior to both UST (OR 3.00; p = 0.009) and TOFA (OR 6.11; p = 0.005) in achieving the primary outcome. Conclusion Even though all three medication demonstrated high efficacy in bio-exposed UC patients, UPA achieved better results at week 16 and 52 in this real-world study. Reference: Singh, Siddharth, et al. “AGA living clinical practice guideline on pharmacological management of moderate-to-severe ulcerative colitis.” Gastroenterology 167.7 (2024): 1307-1343. Conflict of interest: Ms. Camões Neves, Joana: No conflict of interest Costa, Dalila Amélia Amorim: No conflict of interest Cristiano, Margarida: No conflict of interest Portela, Francisco: consulting fees and support from the following companies: Abbvie, Falk, Ferring, Janssen, Lilly, Pfizer, Pharmakern, Takeda and Tillots. Fernandes, Ana Rita: No conflict of interest Fernandes, Samuel Raimundo: No conflict of interest Portugal, Margarida: No conflict of interest Gututui, Madalina: No conflict of interest Paulo, João Pedro: No conflict of interest Gonçalves, Nuno: No conflict of interest Fernandes, Daniela: No conflict of interest Costa, Catarina: No conflict of interest Madureira, Ana Rita: No conflict of interest Vaz Conde, Patrícia: No conflict of interest Damasceno, José: No conflict of interest Guimaraes, Andreia: No conflict of interest Arroja, Bruno: No conflict of interest Goncalves, Raquel: No conflict of interest Leal, Tiago Filipe: No conflict of interest

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Cite This Study

Neves et al. (Thu,) studied this question.

synapsesocial.com/papers/69730f9fc8125b09b0d1f69a https://doi.org/https://doi.org/10.1093/ecco-jcc/jjaf231.806

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